Can Your Brain Have Alzheimer’s Disease, But You Don’t Show Symptoms?

A third to a half of people age 80 and older have symptoms of this disorder.

Can a person have the pathological brain changes associated with Alzheimer's disease and, yet, be totally without symptoms? If so, is there a way to determine if a person's brain has such changes? And if such changes are found, can the illness be stopped in its tracks before further changes lead to clinical symptoms?

As most people know, Alzheimer's disease gradually destroys or changes a person's ability to think, feel, and maintain interest in doing things. A third to a half of people 80 years of age and older have symptoms of this disorder. The size of the elderly population is growing faster than other age groups and, therefore, the number of people with Alzheimer's disease will be increasing dramatically over the next 40 years. In addition to the emotional toll that this devastating illness has on patients and their loved ones, it is responsible for a dramatic financial burden to society.

Alzheimer's disease is likely caused by the abnormal accumulation of a brain chemical called amyloid. Amyloid is made naturally by brain cells. A certain amount is always being produced, and a certain amount is always being eliminated from the fluid that bathes our brain cells. Problems arise when either too much amyloid is made and/or too little amyloid is removed.

Excess amyloid eventually begins to interfere with the ability of brain cells to communicate with each other. After a while, these excessive amounts of amyloid are at least partially responsible for the destruction of brain cells. Although many scientists believe that amyloid is the major culprit in Alzheimer's disease, it is possible that other brain chemicals also contribute to brain cell destruction and clinical symptoms. If amyloid is the major player leading to the changes associated with Alzheimer's disease, then blocking the accumulation of amyloid might prevent the illness. However, if amyloid is only one of several substances that can lead to the destruction of brain cells, then blocking amyloid accumulation may slow or delay the illness, but not prevent it.

So let's return to the original question: Can a person have Alzheimer-type changes in the brain but have no symptoms of the disease? Recent research has clearly demonstrated that the brain can accumulate significant amounts of amyloid before symptoms of Alzheimer's disease begin to occur. This research used clinical interviews and psychological tests to carefully evaluate large numbers of healthy individuals every year until they died. Some of the people participating in this research gave permission for the examination of their brains - in other words, for a brain autopsy - after their deaths. About 20 to 25% of the mentally very healthy people who were over 80 years old at the time of death had brains that showed one of the major hallmarks of Alzheimer's disease - the accumulation of amyloid that is visible with a microscope (called amyloid plaques). Yet, they had no symptoms before they died. This means that the brain can have the changes associated with Alzheimer's disease even though the person remains cognitively and emotionally absolutely fine.

New research suggests that it is likely that amyloid accumulates in the brain for several years before Alzheimer's disease becomes clinically evident, i.e., the brain has the illness, but the person doesn't show symptoms - a state that some researchers call "preclinical Alzheimer's disease." Now, what If there were methods that could be used to determine if amyloid was accumulating in a living person's brain? Then, we would be able to identify individuals who are on the road to developing Alzheimer's disease.

In fact, ongoing studies strongly suggest that researchers can measure brain amyloid in a living person by using certain types of brain imaging procedures. Interestingly, about the same percentage of cognitively healthy, older adults show presumed amyloid accumulation on these scans as is predicted from examining the brains of cognitively healthy, older adults after death. Currently, these imaging techniques are experimental and expensive. More work is also needed to be certain that these methods are truly measuring amyloid in the brain. Nevertheless, if these imaging approaches prove successful, it will open the door for the development of much less expensive technology that will allow doctors to determine if a person is on the way towards developing Alzheimer's disease.

Another approach to detecting preclinical Alzheimer's disease is also showing success. It turns out that at about the same time that imaging procedures are able to visualize amyloid accumulating in a cognitively healthy person's brain, changes are occurring in the level of amyloid in the fluid bathing the brain cells. These levels can be estimated by measuring amyloid in a sample of cerebrospinal fluid (CSF) obtained by using a procedure called a lumbar puncture (LP). (LPs are common procedures that can be done in a neurologist's office and involve inserting a needle into the lower back to remove a bit of the fluid that bathes the spinal cord.) Individuals who show amyloid accumulation in the brain using specialized imaging procedures have decreased levels of amyloid in the CSF. Much like the brain imaging studies, it is still not definite that the changes in CSF amyloid levels are indicative of having (or being on the verge of developing) Alzheimer's disease.

Importantly, these two methods, specialized imaging and measurement of CSF amyloid levels, have the potential to be useful in determining whether an individual is in the process of developing clinical Alzheimer's disease. Further research will clarify whether this potential will become a reality.

But what is the purpose of determining whether someone is developing the clinical illness if there is no treatment available for it? Other research is underway exploring ways to interfere with the accumulation of amyloid. If amyloid is indeed one of the main culprits in causing Alzheimer's disease, then treatments designed to block its accumulation may be able to delay or prevent the illness when given to persons who show Alzheimer-type changes in their brains, but who are not yet clinically symptomatic. A variety of treatments targeting amyloid are at various stages of testing.

The purpose of this post is to alert readers to clinically relevant progress in the potential diagnosis and treatment of one of the world's most devastating neuropsychiatric disorders - Alzheimer's disease. Researchers are always thrown curve balls - unexpected findings that can force them to modify their approaches. However, we are optimistic that progress will continue to be made and will lead to effective treatments for this terrible disease.

This column was co-written by Eugene Rubin MD, PhD and Charles Zorumski MD. Neither have financial conflicts of interests involving either the pharmaceutical industry or the device-manufacturing industry.